crossing96/oncoscreening huggingface dataset:
Interplay of IL-6, GDF-15 and Sarcopenia in Patients With Bladder Cancer Undergoing Radical Cystectomy and Its Implications on Survival.	BACKGROUND: Sarcopenia has emerged as a significant predictor of adverse outcomes in cancer. Specifically, this is also true for patients with bladder cancer undergoing radical cystectomy (RC). This retrospective study investigates the roles of the biomarkers interleukin-6 (IL-6) and growth differentiation factor-15 (GDF-15), in the context of sarcopenia, assessing their impact on oncological and survival outcomes. METHODS: Preoperative serum IL-6 and GDF-15 levels were analysed in 179 patients undergoing RC. Their association with sarcopenia, adverse pathological features and survival outcomes was investigated. RESULTS: Elevated IL-6 and GDF-15 levels were significantly correlated with the presence of sarcopenia (p = 0.04 and p = 0.03, respectively). IL-6 and GDF-15 levels in serum showed a positive correlation (Spearman r = 0.45, 95%CI 0.32-0.56, p < 0.01). Higher IL-6 and GDF-15 levels were also associated with higher tumour stages (both p < 0.01), positive lymph nodes (p = 0.02 and p < 0.01) and unfavourable surgical margins (both p < 0.01). Patients with both sarcopenia and high IL-6 or GDF-15 levels exhibited significantly worse overall survival and cancer-specific survival in multivariate Cox regression analysis. CONCLUSIONS: These findings highlight the interplay between IL-6, GDF-15, sarcopenia and tumour progression, suggesting that IL-6 and GDF-15 may serve as valuable prognostic biomarkers and potential therapeutic targets. Further research is warranted to explore targeted therapeutic strategies aimed at mitigating sarcopenia and systemic inflammation in this patient population.	bladder
FAM174B remodels the tumor microenvironment, inhibits the infiltration of macrophage, predicts the molecular subtype and therapeutic response of bladder cancer.	Background: While the immunomodulatory function of FAM174B in bladder cancer (BLCA) has yet to be fully elucidated, elucidating its biological mechanisms could potentially enhance immunotherapeutic outcomes for this malignancy. Methods: Bulk RNA-seq data from TCGA and GEO databases were analyzed to investigate FAM174B expression patterns and immune landscape characteristics in pan-cancer. The immunoregulatory role of FAM174B in BLCA was systematically evaluated through immune infiltration analysis, immunomodulator profiling, cancer-immunity cycle assessment, and immune checkpoint examination. Validation was performed using the IMvigor210 immunotherapy cohort and a combined GEO dataset (n=871). A machine learning-based immune-related signature was developed for prognostic and therapeutic response prediction. Results: FAM174B was highly expressed in cancer tissues across multiple human cancer types including BLCA. Specifically, FAM174B negatively correlated with various immunological features including immunoregulators and immune cell infiltration abundances, suggesting that FAM174B remodeled the microenvironment to a non-inflamed phenotype of BLCA. Besides, patients with high-FAM174B expression may process limited sensitivity to immunotherapy and increased likelihood of hyperprogression. Consensus molecular classification analysis indicated that elevated FAM174B is related to a luminal BLCA subtype which was characterized by reduced immune infiltration, inhibited immuno- and chemo-therapeutic responses, yet increased response to angiogenesis inhibitors and targeted therapy. Furthermore, the immune-related signature, formulated through a machine learning-integrated approach, is shown to be a dependable indicator for predicting cancer prognosis and the efficacy of immunotherapy responses for BLCA. Conclusion: Given the pivotal role of FAM174B in shaping the non-inflamed tumor microenvironment of BLCA, therapeutic targeting of FAM174B may represent a promising strategy for BLCA management. Furthermore, FAM174B expression could serve as a potential biomarker for predicting molecular subtypes and treatment responsiveness in BLCA patients.	bladder
Integrating Spatial Multi-Omics and Machine Learning to Unravel the Role of PANoptosis in Bladder Cancer Prognosis and Immunotherapy Response.	Background: Studies have reported the special value of PANoptosis in cancer, but there is no study on the prognostic and therapeutic effects of PANoptosis in bladder cancer (BLCA). This study aimed to explore the role of PANoptosis in BLCA heterogeneity and its impact on clinical outcomes and immunotherapy response while establishing a robust prognostic model based on PANoptosis-related features. Methods: Gene expression profiles and clinical data were collected from public databases. Spatial heterogeneity of cell death pathways in BLCA was evaluated. Consensus clustering was performed based on identified PANoptosis genes. Cell death pathway scores, molecular, and pathway activation differences between different groups were compared. Protein-protein interaction (PPI) network construction was constructed, and immune-related gene sets, tumor immune dysfunction and exclusion (TIDE) scores, and SubMap analysis were used to evaluate immunomodulator expression and immunotherapy efficacy. Ten machine learning algorithms were utilized to develop the most accurate predictive risk model, and a nomogram was created for clinical application. Results: BLCA demonstrated a spatially heterogeneous distribution of pyroptosis, apoptosis, and necroptosis. Notably, T effector cells significantly colocalized with total apoptosis. Two PANoptosis modes were identified: high PANoptosis (high. PANO) and low PANoptosis (low. PANO). High. PANO was associated with worse clinical outcomes and advanced tumor stage, and increased activation of immune-related and cell death pathways. It also showed increased infiltration of immune cells, elevated expression of immunomodulatory factors, and enhanced responsiveness to the immunotherapy. The PANoptosis-related machine learning prognostic signature (PMLS) exhibited strong predictive power for outcomes in BLCA. CSPG4 was identified as a key gene underlying prognostic and therapeutic differences. Conclusion: PANoptosis shapes distinct prognostic and immunological phenotypes in BLCA. PMLS offers a reliable prognostic tool. CSPG4 may represent a potential therapeutic target in PANoptosis-driven BLCA.	bladder
Decoding bladder cancer aggressiveness: A proteomic, phosphoproteomic and metabolomic approach.	BACKGROUND: Bladder cancer (BC) is the most common malignancy of the urinary system. However, the median survival of patients with metastatic bladder cancer remains limited. Thus, there is an urgent imperative to develop novel biomarkers for BC-targeted therapies and to conduct in-depth investigations into BC pathogenesis leveraging multi-omics technologies. RESULTS: Our results revealed that proteins co-upregulated in both proteomic and phosphoproteomic analysis, such as SLC4A7 and MYO9B, demonstrated potential utility in distinguishing MIBC from NMIBC. Upregulation of CPT2 and palmitic acid in MIBC patients highlighted the dysregulation of physiological control mechanisms and enhanced pro-tumorigenic effects of lipid metabolic pathways. CONCLUSIONS: Integrated multi-omics analysis reveals that key regulatory proteins such as SLC4A7 and MYO9B play pivotal roles in mediating the aggressive phenotypes of MIBC. Aberrant upregulation of CPT2 protein and metabolites like palmitic acid may drive malignant transformation from NMIBC to MIBC by promoting lipid metabolic reprogramming. SIGNIFICANCE: This study utilized LC-MS/MS to systematically profile the proteomic, phosphoproteomic, and metabolomic characteristics of MIBC, NMIBC, and adjacent noncancerous tissues, with the aim of identifying key molecules and metabolites driving bladder cancer progression. Our findings indicate that aberrant phosphorylation of regulatory proteins such as SLC4A7 and MYO9B may play a critical role in mediating the invasive phenotype of MIBC. In parallel, the upregulation of CPT2 and its associated metabolites (e.g., palmitic acid) suggests that lipid metabolic reprogramming, including enhanced β-oxidation and membrane phospholipid synthesis, may contribute to the malignant transition from NMIBC to MIBC. Overall, this study not only reveals potential molecules and metabolites driving bladder cancer progression but also provides a valuable reference for further exploration of pathways associated with bladder cancer invasiveness.	bladder
[Prognostic analysis of laparoscopic simultaneous radical cystectomy and nephroureterectomy].	OBJECTIVE: To investigate the safety and prognostic factors influencing the treatment of upper urinary tract urothelial carcinoma (UTUC) combined with bladder cancer (BCa) by laparoscopic simultaneous radical cystectomy and nephroureterectomy (RCNU). METHODS: The clinical data of patients admitted to Peking University Third Hospital for laparoscopic RCNU surgery from January 2009 to September 2023 were analyzed retrospectively. Based on the same gender, age (±5 years), history of uroepithelial tumors, underlying diseases, T-stage, N-stage, M-stage, American Society of Anesthesiologists (ASA) score, Charlson comorbidity index, and body mass index (BMI) (±5), 34 patients with RCNU were matched 1 ∶1 with patients with bladder cancer who underwent laparoscopic radical cystectomy (RC) alone. Kaplan-Meier survival analysis was used to calculate patient survival, and Cox proportional regression risk model was used to analyze clinical factors affecting prognosis. RESULTS: Of the 68 patients enrolled, the follow-up rate was 100% with a median follow-up time of 27.0 (11.7, 60.2) months. Comparison of intraoperative conditions (including operation time, estimated intraoperative bleeding, intra-operative blood transfusion, etc.) between the two groups of patients showed no significant difference (P>0.05). Comparison of preoperative creatinine and postoperative creatinine between the two groups of patients showed significant differences (P < 0.05). The perioperative Clavien grade Ⅲ-Ⅳ complication rates were 2.9% (1/34) in the RC group and 5.9% (2/34) in the RCNU group. There was no significant difference in terms of perioperative complications between the two groups. Overall survival was significantly lower in the patients receiving RCNU compared with the matched group receiving RC alone (P < 0.05). Cox regression analysis suggested that two factors, high N stage and high postoperative creatinine, were independent risk factors affecting the prognosis of patients in the 2 groups (P < 0.05). CONCLUSION: The overall survival prognosis of patients undergoing RCNU surgery was worse compared with laparoscopic RC surgery alone during the same period. There was no clinically significant difference between the two groups in terms of operation time, intraoperative bleeding, and perioperative complications, and there were clinically significant differences in preoperative renal function and post-operative renal function.	bladder
Enfortumab vedotin promotes PD-L1 expression in urothelial carcinoma via NF-κB and STAT3 pathways highlighting mechanisms of immune evasion and potential for combination therapy.	BACKGROUND: PD-1/PD-L1 inhibitors have revolutionized urothelial carcinoma (UC) treatment; however, the effects of prior or concurrent therapies on PD-L1 regulation remain unclear. This study investigates whether enfortumab vedotin (EV), a nectin-4-targeting antibody-drug conjugate, modulates PD-L1 expression in UC cells, and explores the underlying molecular pathways. METHODS: UC cell lines RT4 (high nectin-4 expression) and T24 (low nectin-4 expression) were treated with EV (10 µg/ml) for 6, 12, or 24 h, followed by a 48-hour drug-free period. Protein and mRNA expression levels of PD-L1, NF-κB, and STAT3 were quantified using western blotting and qRT-PCR. RESULTS: EV treatment upregulated PD-L1, NF-κB, and STAT3 in a time-dependent manner, with a more pronounced effect observed in RT4 than in T24 cells. PD-L1 protein levels increased 0.761-fold (12 h) and 2.399-fold (24 h) in RT4, whereas T24 showed a decrease (0.517-fold at 12 h) or minimal change (0.006-fold at 24 h). NF-κB expression increased 64.42-fold (12 h) and 97.03-fold (24 h) in RT4, compared to 1.251-fold (12 h) and 1.210-fold (24 h) in T24. STAT3 levels rose 2.334-fold (12 h) and 2.844-fold (24 h) in RT4, whereas T24 showed increases of 1.620-fold (12 h) and 1.379-fold (24 h). At the mRNA level (6 h post-treatment), PD-L1, NF-κB, and STAT3 were upregulated by 1.228-, 1.332-, and 1.225-fold, respectively, in RT4 cells. CONCLUSION: EV is associated with increased PD-L1 expression, along with upregulation of NF-κB and STAT3, suggesting a mechanistic link that may contribute to immune modulation in nectin-4-high bladder cancer cells. These findings highlight the need for combination strategies integrating EV with PD-1/PD-L1 inhibitors to optimize therapeutic outcomes in UC.	bladder
Inlexzo (gemcitabine intravesical system): promising data but key questions remain.	The FDA approval of Inlexzo (gemcitabine intravesical system, formerly TAR-200) for BCG-refractory non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ is a milestone achievement in bladder-sparing therapy. Outcomes from the SunRISe-1 trial showed an outstanding 3-month complete response rate of 82%, and sustainability in more than half of responders at 12 months. Yet enthusiasm must be balanced with significant cautions: lack of comparator arm, immature long-term survival data, and practical issues with indwelling intravesical delivery, risk of infection, and access in low-resource environments. While Inlexzo is promising in a population where alternatives are scarce, its place must be clarified by longer-term follow-up, randomized comparisons versus systemic and intravesical therapies, and real-world experience. Prior to that, clinicians must utilize open counseling and shared decision-making.	bladder
Bladder Preservation in Muscle-Invasive Bladder Cancer: A Population-Based Analysis from British Columbia.	Bladder cancer is the 5th most common cancer in Canada and a quarter of diagnosed patients have muscle-invasive bladder cancer (MIBC). Standard treatment options, systemic therapy and radical cystectomy (RC) are associated with high rates of adverse outcomes. Recently, trimodal treatment (TMT), a bladder preservation strategy defined as maximal transurethral resection of bladder tumor (TURBT) and chemoradiation, has been considered an alternative per guidelines for select patients who prefer bladder preservation or those with comorbidities. Nevertheless, the uptake of bladder preservation strategies in Canada remains low. We conducted a retrospective evaluation in British Columbia (BC) to assess the real-world outcomes of bladder-sparing radiotherapy. Cohort treated with combined chemoradiotherapy (concurrent and/or adjuvant, neoadjuvant chemotherapy) showed numerical improvements across all evaluated endpoints, including disease-specific survival and progression-free survival, compared with radiation therapy alone, which is generally considered an inferior strategy. However, these differences did not reach statistical significance, contrasting with the literature. Despite the limitations posed by the small sample size and the study's retrospective design, the findings highlight the pivotal role of appropriate patient selection in achieving meaningful therapeutic outcomes. Future studies integrating biomarker-driven strategies are needed to enhance outcomes through individualized treatment selection, particularly for older patients with multiple comorbidities.	bladder
Comparative histologic survey and transcriptomic investigation into canine prostate carcinoma.	Dogs share features in prostate gland anatomy, physiology, and pathology with men. However, human and canine prostate carcinoma (PC) have histologic and molecular differences. Particularly, the histogenesis of canine PC (cPC) is unclear. This study investigated the origin of cPC using histopathology and transcriptomics with comparison to men. Prostate glands retrospectively and prospectively collected from 445 dogs (approximately 95 % autopsy samples) were surveyed for early carcinomas and preneoplastic lesions, particularly high-grade prostatic intraepithelial neoplasia (HGPIN) due to its role in the pathogenesis of PC in men. Lineage gene signatures defining prostate luminal epithelium and urothelium were identified for inter- and intraspecies RNA-sequencing comparisons, including between cPC and canine urinary bladder urothelial carcinoma (UC). Postmortem prostate lesion frequencies were similar to previously reported canine studies. Intraductal/intra-acinar growth (31/35; 88.6 %) was common in representative samples of cPC. Prostate epithelial changes consistent with HGPIN in men were not observed. Proliferative lesions and early carcinomas were rare (7/445; 1.6 %). Patterns in prostate and urothelium marker gene expression signatures differed between human and canine PC. Compared to non-neoplastic prostate gland, cPC had significantly decreased prostate-specific and increased urothelium gene signatures. The results suggest many cases diagnosed as cPC are UC or have urothelial differentiation and thus differ from PC in men, with important implications for canine tumor classification and translational studies.	bladder
Identification of TRIM59 as a Key Biomarker for Ferroptosis Resistance and Immunotherapy Response in Bladder Cancer via Multi-Omics Integration and Machine Learning.	BACKGROUND: Bladder cancer (BCa) is a highly heterogeneous malignancy, and precision treatment remains challenging. Identifying molecular biomarkers and risk factors is essential for improving prognosis and therapeutic strategies. METHODS: We integrated expression quantitative trait loci (eQTL) data with Mendelian randomization (MR) analysis to identify candidate risk genes associated with BCa. Subsequently, a prognostic risk model was developed using machine learning methods to explore its correlation with molecular features, immune cell infiltration, and ferroptosis-related pathways. Based on these findings, the Tripartite Motif Containing 59 (TRIM59) protein was selected for further experimental validation. The functional role of TRIM59 in BCa progression was further investigated using MTT assays in BCa cell lines. Additionally, western blotting (WB) was conducted to confirm the potential association between TRIM59 expression and ferroptosis regulation. RESULTS: The risk model identified distinct signaling pathways that differentiate the high-risk and low-risk BCa groups. The low-risk group demonstrated greater infiltration of CD8+ T cells. Conversely, the high-risk group exhibited enhanced immune evasion, as evidenced by increased infiltration of macrophages and fibroblasts. Furthermore, TRIM59 exerts a regulatory influence on ferroptosis progression in BCa by modulating key genes involved in this process, including Solute Carrier Family 7 Member 11 (SLC7A11), Glutathione Peroxidase 4 (GPX4), and Acyl-CoA Synthetase Long Chain Family Member 4 (ACSL4). CONCLUSION: Our integrative approach highlights the potential of genomic and immune microenvironment data in developing personalized risk models for BCa, offering insights into individualized treatment strategies. Importantly, TRIM59 is involved in ferroptosis resistance in BCa. These findings have potential implications for identifying diagnostic biomarkers and therapeutic targets for BCa treatment.	bladder
Male reproductive and sexual health outcomes following intravesical therapy for non-muscle invasive bladder cancer.	PURPOSE: Non-muscle-invasive bladder cancer (NMIBC) is primarily treated with intravesical Bacillus Calmette-Guerin (BCG) immunotherapy or chemotherapy. While these therapies effectively reduce tumor recurrence and progression, their impact on male reproductive health remains underexplored. This review synthesizes current evidence on the reproductive effects of intravesical therapies in men with NMIBC. METHODS: A structured PubMed search was conducted to identify studies evaluating the effects of intravesical therapy on male reproduction. Studies published in English between 2000 and 2025 were screened. Outcomes related to semen parameters, hormonal changes, and sexual function were extracted from selected studies. RESULTS: Preclinical studies have demonstrated that exposure to intravesical agents may result in reversible testicular damage. In clinical settings, although data are limited, BCG therapy has been associated with transient impairments in semen parameters and sexual function, while reproductive hormone levels generally remain stable, suggesting a localized rather than systemic effect. Although intravesical chemotherapy exhibits minimal systemic absorption, concerns regarding its potential gonadotoxicity persist, and clinical data on its impact on male reproductive health remain limited. Furthermore, newly approved agents for NMIBC, such as nadofaragene and nogapendekin alfa inbakicept-pmln, currently lack fertility-related safety data. Genitourinary complications following intravesical therapy, including epididymo-orchitis, and prostatitis, may further compromise the integrity of the male reproductive tract and exacerbate fertility risks. CONCLUSION: With fatherhood increasingly occurring beyond age 40, uro-oncologists should consider the potential effects of intravesical therapy on male fertility and sexual function. Expanding research into reproductive outcomes among NMIBC patients may support more informed counseling on this matter.	bladder
A novel sono-activatable nanoreactor induces precision intratumoral juglone generation and caspase 3/GSDME-mediated pyroptosis for treatment of bladder cancer.	"BACKGROUND: Juglone, a natural naphthoquinone compound, exhibits potent anticancer activity but faces clinical limitations due to poor solubility, low bioavailability, and systemic toxicity. While tumor microenvironment-responsive drug activation strategies offer a promising solution, achieving precise spatial control over the conversion of non-toxic precursors into cytotoxic agents remains a significant challenge. METHODS: We developed DHN@Pt/PtMBCPsNSs, a platinum (Pt)-methylene blue (MB)- based nanoscale sonosensitizer, to enable ultrasound-triggered on-demand juglone synthesis within tumors. The system was evaluated in bladder cancer models including cell lines, patient-derived organoids (PDOs) and patient-derived tumor xenograft (PDX) models, assessing tumor uptake, intracellular distribution, hypoxia modulation (""H(2)O(2)-O(2)-¹O(2)"" cascade), oxidative stress markers (SOD, GSH, MDA, GSSG), and cell death pathways (apoptosis/pyroptosis). Transcriptome sequencing was performed to elucidate molecular mechanisms. RESULTS: DHN@Pt/PtMBCPsNSs were internalized by UMUC-3 and T24 cells and primarily accumulated within the mitochondrial compartments. The platinum-based components catalytically exhausted GSH via redox cycling. DHN@Pt/PtMBCPsNSs triggered the production of O(2) and ¹O(2) after local US irradiation, alleviating hypoxia and selectively converting dihydroxynaphthalene (DHN) to juglone in tumors, which reducing the systemic toxicity of juglone. The nanosystem further disrupted cellular redox balance by triggering depletion of antioxidant defenses (SOD and GSH) and reducing the ratio of GSH/GSSG. In vitro cell experiments and PDOs experiments demonstrated that DHN@Pt/PtMBCPsNSs combined with US irradiation can significantly inhibit bladder cancer cell proliferation, induce apoptosis, and regulate pyroptosis via the ROS-mediated caspase 3/GSDME signaling pathway. In the PDX model, DHN@Pt/PtMBCPsNSs accumulated at the tumor site and significantly inhibited tumor growth under US irradiation. CONCLUSIONS: As a novel sonosensitizer and pyroptosis inducer, DHN@Pt/PtMBCPsNSs achieve a precise synergistic effect of chemotherapy and sonodynamic therapy within cells, while minimizing adverse effects on normal cells and overcoming the limitations associated with natural chemotherapeutic agents. This approach may advance clinical translation of natural anticancer agents."	bladder